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Background <p>Primary rare headache conditions, like Trigeminal Autonomic Cephalalgias (TACs) and Cluster Headache (CH), affect less than 0.1% of the total population worldwide. Even though they are rare, they cause substantial physical and socioeconomic burdens, and many patients experience refractoriness, contraindications, poor tolerability, or incomplete response to established therapies. Recent studies have focused on the use of Botulinum Toxin (BoNT) as a neuromodulatory agent for the treatment of patients resistant to conventional medication for TACs.</p> Methods <p>We conducted a narrative review of PubMed and Scopus for English-language publications on BoNT in rare primary headache disorders through March 2025, including clinical trials, cohort studies, case series, and case reports; reference lists of eligible articles were also screened.</p> Results <p>At present, nearly all the research produced is of low quality, such as open trials and case series. The efficacy of Botulinum Toxin varies, but it seems to trigger a 50% attack reduction in patients with Cluster Headache. Its application in the case of Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and tearing (SUNCT) patients is purely anecdotal. It acts by inhibiting SNAP-25–mediated release of neuropeptides, including Calcitonin Gene-Related Peptide (CGRP), which play a key role in pain transmission.</p> Conclusion <p>The use of Botulinum Toxin is promising, representing a safe adjunctive treatment option for patients with refractory rare headache disorders. There is a need to test it through controlled trials, thereby standardizing the measures and effectiveness of the agent.</p>

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Unlocking Relief: Botulinum Toxin’s Role in Conquering Rare Primary Headaches- A Narrative Exploration

  • 期刊论文

  • 发表日期：

    2026年6月1日

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  • Reza Mosaddeghi-Heris,
  • Nasrin Forghani,
  • Hadi Sahrai,
  • Duha Yahya,
  • Ali Norouzi,
  • Paolo Martelletti,
  • Sima Osouli Meinagh

摘要

Background

Primary rare headache conditions, like Trigeminal Autonomic Cephalalgias (TACs) and Cluster Headache (CH), affect less than 0.1% of the total population worldwide. Even though they are rare, they cause substantial physical and socioeconomic burdens, and many patients experience refractoriness, contraindications, poor tolerability, or incomplete response to established therapies. Recent studies have focused on the use of Botulinum Toxin (BoNT) as a neuromodulatory agent for the treatment of patients resistant to conventional medication for TACs.

Methods

We conducted a narrative review of PubMed and Scopus for English-language publications on BoNT in rare primary headache disorders through March 2025, including clinical trials, cohort studies, case series, and case reports; reference lists of eligible articles were also screened.

Results

At present, nearly all the research produced is of low quality, such as open trials and case series. The efficacy of Botulinum Toxin varies, but it seems to trigger a 50% attack reduction in patients with Cluster Headache. Its application in the case of Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and tearing (SUNCT) patients is purely anecdotal. It acts by inhibiting SNAP-25–mediated release of neuropeptides, including Calcitonin Gene-Related Peptide (CGRP), which play a key role in pain transmission.

Conclusion

The use of Botulinum Toxin is promising, representing a safe adjunctive treatment option for patients with refractory rare headache disorders. There is a need to test it through controlled trials, thereby standardizing the measures and effectiveness of the agent.